The Effects of Chiropractic Spinal Adjustment on EEG in Adults with Alzheimer's and Parkinson's Disease: A Pilot Randomised Cross-over Trial.

OBJECTIVES: In this study, we explored the effects of chiropractic spinal adjustments on resting-state electroencephalography (EEG) recordings and early somatosensory evoked potentials (SEPs) in Alzheimer's and Parkinson's disease. METHODS: In this randomized cross-over study, 14 adults with Alzheimer's disease (average age 67 ± 6 years, 2 females:12 males) and 14 adults with Parkinson's disease (average age 62 ± 11 years, 1 female:13 males) participated. The participants underwent chiropractic spinal adjustments and a control (sham) intervention in a randomized order, with a minimum of one week between each intervention. EEG was recorded before and after each intervention, both during rest and stimulation of the right median nerve. The power-spectra was calculated for resting-state EEG, and the amplitude of the N30 peak was assessed for the SEPs. The source localization was performed on the power-spectra of resting-state EEG and the N30 SEP peak. RESULTS: Chiropractic spinal adjustment significantly reduced the N30 peak in individuals with Alzheimer's by 15% (p = 0.027). While other outcomes did not reach significance, resting-state EEG showed an increase in absolute power in all frequency bands after chiropractic spinal adjustments in individuals with Alzheimer's and Parkinson's disease. The findings revealed a notable enhancement in connectivity within the Default Mode Network (DMN) at the alpha, beta, and theta frequency bands among individuals undergoing chiropractic adjustments. CONCLUSIONS: We found that it is feasible to record EEG/SEP in individuals with Alzheimer's and Parkinson's disease. Additionally, a single session of chiropractic spinal adjustment reduced the somatosensory evoked N30 potential and enhancement in connectivity within the DMN at the alpha, beta, and theta frequency bands in individuals with Alzheimer's disease. Future studies may require a larger sample size to estimate the effects of chiropractic spinal adjustment on brain activity. Given the preliminary nature of our findings, caution is warranted when considering the clinical implications. CLINICAL TRIAL REGISTRATION: The study was registered by the Australian New Zealand Clinical Trials Registry (registration number ACTRN12618001217291 and 12618001218280).

Synthesis of Competitive and Noncompetitive Inhibitors of Alpha-Glucosidase and Anticancer Agents.

Imidazoles and phenylthiazoles are an important class of heterocycles that demonstrate a wide range of biological activities against various types of cancers, diabetes mellitus and pathogenic microorganisms. The heterocyclic structure having oxothiazolidine moiety is an important scaffold present in various drugs, with potential for enzyme inhibition. In an effort to discover new heterocyclic compounds, we synthesized 26 new 4,5-diphenyl-1H-imidazole, phenylthiazole, and oxothiazolidine heterocyclic analogues that demonstrated potent α-glucosidase inhibition and anticancer activities. Majority of the compounds noncompetitively inhibited α-glucosidase except for two that exhibited competitive inhibition of the enzyme. Docking results suggested that the noncompetitive inhibitors bind to an apparent allosteric site on the enzyme located in the vicinity of the active site. Additionally, the analogues also exhibited significant activity against various types of cancers including non-small lung cancer. Since tubulin protein plays an important role in the pathogenesis of non-small lung cancer, molecular docking with one of the target compounds provided important clues to its binding mode. The current work on imidazoles and phenylthiazole derivatives bears importance for designing of new antidiabetic and anticancer drugs.

Mapping of antibody epitopes based on docking and homology modeling.

Antibodies are key proteins produced by the immune system to target pathogen proteins termed antigens via specific binding to surface regions called epitopes. Given an antigen and the sequence of an antibody the knowledge of the epitope is critical for the discovery and development of antibody based therapeutics. In this work, we present a computational protocol that uses template-based modeling and docking to predict epitope residues. This protocol is implemented in three major steps. First, a template-based modeling approach is used to build the antibody structures. We tested several options, including generation of models using AlphaFold2. Second, each antibody model is docked to the antigen using the fast Fourier transform (FFT) based docking program PIPER. Attention is given to optimally selecting the docking energy parameters depending on the input data. In particular, the van der Waals energy terms are reduced for modeled antibodies relative to x-ray structures. Finally, ranking of antigen surface residues is produced. The ranking relies on the docking results, that is, how often the residue appears in the docking poses' interface, and also on the energy favorability of the docking pose in question. The method, called PIPER-Map, has been tested on a widely used antibody-antigen docking benchmark. The results show that PIPER-Map improves upon the existing epitope prediction methods. An interesting observation is that epitope prediction accuracy starting from antibody sequence alone does not significantly differ from that of starting from unbound (i.e., separately crystallized) antibody structure.

Ternary Lithium Nickel Boride with 1D Rapid-Ion-Diffusion Channels as an Anode for Use in Lithium-Ion Batteries.

Anode materials with high-rate performances and good electrochemical stabilities are urgently required for the grid-scale application of lithium-ion batteries (LIBs). Theoretically, transition metal borides are desirable candidates because of their appropriate working potentials and good conductivities. However, the reported metal borides exhibit poor performances owing to their lack of favorable Li+ storage sites and poor structural stabilities during long-term charging/discharging. In this work, a ternary alkali metal boride, Li1.2 Ni2.5 B2 , which displays a high Li+ storage capacity and remarkable electrochemical stability and an excellent rate performance is studied. In contrast to conventional transition metal borides, the introduction of Li atoms facilitates the formation of 1D Ni/B-based honeycomb channels during synthesis. This Ni/B framework successfully sustains the strain during Li+ intercalation and deintercalation, and thus, the optimized Li1.2 Ni2.5 B2 anode exhibits an excellent cycle stability over 500 charge/discharge cycles. This electrode also exhibits superior reversible capacities of 350, 183, and 80 mA h g-1 at 0.1, 1, and 5 A g-1 , respectively, indicating the considerable potential of the 1D Ni/B framework as a commercially available fast-charging LIB anode.

In-Situ Construction of V2 O5 Nanosheet/Nitrogen-Doped Carbon Nanosheet Heterostructures with Interfacial C─O Bridging Bonds as the Cathode Material for Zn Ion Batteries.

Layered oxides are widely used as the electrode materials for metal ion batteries. However, for large radius size ions, such as Zn2+ and Al3+ , the tightly stacked layers and poor electrical conductivity of layered oxides result in restricted number of active sites and sluggish reaction kinetics. In this work, a facile in-situ construction strategy is provided to synthesize layered oxide nanosheets/nitrogen-doped carbon nanosheet (NC) heterostructure, which shows larger interlayer spacing and better electrical conductivity than the layered oxides. As a result, the Zn2+ ion diffusion inside the interlayer gallery is greatly enhanced and the storage sites inside the gallery can be better used. Meanwhile, the NC layers and oxide nanosheets are bridged by the C─O bonds to form a stable structure, which contributes to a better cycling stability than the pure layered oxides. The optimal V2 O5 @NC-400 cathode shows a capacity of 467 mA h g-1 at 0.1 A g-1 for 300 cycles, and long-term cyclic stability of 4000 cycles at 5 A g-1 with a capacity retention of 92%. All these performance parameters are among the best for vanadium oxide-based cathode materials.

Synthesis of new compounds bearing methyl sulfonyl pharmacophore as selective COX-2 inhibitor.

Cyclooxygenase, also known as prostaglandin H2 synthase (PGH2), is one of the most important enzymes in pharmacology because inhibition of COX is the mechanism of action of most nonsteroidal anti-inflammatory drugs. In this study, ten thiazole derivative compounds had synthesized. The analysis of the obtained compounds was performed by 1 H NMR and 13 C NMR methods. By this method, the obtained compounds could be elucidated. The inhibitory effect of the obtained compounds on cyclooxygenase (COX) enzymes was investigated. The encoded compounds 5a, 5b, and 5c were found to be the most potent compared to the reference compounds ibuprofen (IC50 = 5.589 ± 0.278 µM), celecoxib (IC50 = 0.132 ± 0.004 µM), and nimesulide (IC50 = 1.692 ± 0.077 µM)against COX-2 isoenzyme. The inhibitory activity of 5a, 5b, and 5c is approximate, but the 5a derivative proved to be the most active in the series with an IC50 value of 0.180 ± 0.002 µM. The most potent COXs inhibitor was 5a, which was further investigated for its potential binding mode by a molecular docking study. Compound 5a was found to be localized at the active site of the enzyme, like celecoxib, which has a remarkable effect on COXs enzymes.

Social support and perceived uncertainties during COVID-19: Consequences for employees' wellbeing.

The COVID-19 crisis has drastically affected organizations worldwide, thereby influencing the employees' psychological wellbeing. Since it is a new pandemic, research is sparse in the domain of employees' psychological wellbeing in relation to the phenomenon. Drawing on social support and job demand-resource perspectives, this research adds to the factors affecting employees' wellbeing due to the coronavirus outbreak. Specifically, this study is an investigation of co-workers' instrumental support in predicting employees' emotional exhaustion via employees' perceived uncertainties experienced due to the COVID-19 pandemic. Further, we tested for the contextual specificity of family support on uncertainties and its link with employees' emotional exhaustion. With data drawn from two universities (n = 275), the findings reveal a negative association between co-worker task support and an employee's emotional exhaustion, and an employee's perceived uncertainties mediate this relationship. Moreover, the moderating analysis exhibits that family support mitigates the negative effect of uncertainty perception on emotional exhaustion. Our study reveals that coworker and family support are extremely important during the COVID-19 pandemic. These findings are equally valuable for organizations and society to mitigate the detrimental effects of the COVID-19 pandemic on employees' wellbeing.

MXenes as Emerging Materials: Synthesis, Properties, and Applications.

Due to their unique layered microstructure, the presence of various functional groups at the surface, earth abundance, and attractive electrical, optical, and thermal properties, MXenes are considered promising candidates for the solution of energy- and environmental-related problems. It is seen that the energy conversion and storage capacity of MXenes can be enhanced by changing the material dimensions, chemical composition, structure, and surface chemistry. Hence, it is also essential to understand how one can easily improve the structure-property relationship from an applied point of view. In the current review, we reviewed the fabrication, properties, and potential applications of MXenes. In addition, various properties of MXenes such as structural, optical, electrical, thermal, chemical, and mechanical have been discussed. Furthermore, the potential applications of MXenes in the areas of photocatalysis, electrocatalysis, nitrogen fixation, gas sensing, cancer therapy, and supercapacitors have also been outlooked. Based on the reported works, it could easily be observed that the properties and applications of MXenes can be further enhanced by applying various modification and functionalization approaches. This review also emphasizes the recent developments and future perspectives of MXenes-based composite materials, which will greatly help scientists working in the fields of academia and material science.

Assessing the binding properties of CASP14 targets and models.

An important question is how well the models submitted to CASP retain the properties of target structures. We investigate several properties related to binding. First we explore the binding of small molecules as probes, and count the number of interactions between each residue and such probes, resulting in a binding fingerprint. The similarity between two fingerprints, one for the X-ray structure and the other for a model, is determined by calculating their correlation coefficient. The fingerprint similarity weakly correlates with global measures of accuracy, and GDT_TS higher than 80 is a necessary but not sufficient condition for the conservation of surface binding properties. The advantage of this approach is that it can be carried out without information on potential ligands and their binding sites. The latter information was available for a few targets, and we explored whether the CASP14 models can be used to predict binding sites and to dock small ligands. Finally, we tested the ability of models to reproduce protein-protein interactions by docking both the X-ray structures and the models to their interaction partners in complexes. The analysis showed that in CASP14 the quality of individual domain models is approaching that offered by X-ray crystallography, and hence such models can be successfully used for the identification of binding and regulatory sites, as well as for assembling obligatory protein-protein complexes. Success of ligand docking, however, often depends on fine details of the binding interface, and thus may require accounting for conformational changes by simulation methods.

Thiosemicarbazide binds with the dicopper center in the competitive inhibition of mushroom tyrosinase enzyme: Synthesis and molecular modeling of theophylline analogues.

Theophylline is long known for its anti-ageing and anti-oxidative properties. Moreover, Tyrosinase is a crucial enzyme that regulates the melanin synthetic pathway, which is involved in various physiological metabolic processes including aging. The current paper describes the synthesis of various heterocyclic systems coupled with theophylline moiety along with their tyrosinase inhibition activity in view to identify the potent nucleus. Around 19 compounds were synthesized and screened for enzyme inhibition. Based on the current study, it is suggested that compound 18 having thiosemicarbazide has strong enzyme inhibition potential. The enzyme kinetics and docking studies provide important insights into how the compound interacts with the mushroom tyrosinase active site. The work will provide clue to developing new, potent tyrosinase inhibitors for drug development.

Intracranial hemorrhage complicating anticoagulant prophylactic therapy in three hospitalized COVID-19 patients.

SARS-CoV2 has led to a global pandemic affecting almost 3 million people in almost over 3 months. Various clinical presentations have been reported so far and no definite therapy is established. Anticoagulation is recommended by several experts to address the potential prothrombotic complications from COVID-19, but its safety and regimen need further clinical trials and safety and efficacy profile. Here, we present three cases of intracranial hemorrhage in three critically ill patients with COVID-19 and discuss their course in relation to various regimens of anticoagulation used.

Phylogenetic Characterization of the 5' Untranslated Region of Untypable HCV Genotypes Circulating in Pakistan.

INTRODUCTION: Commercial methods for HCV genotyping is challenged by the increased prevalence of untypable genotypes in Pakistan. OBJECTIVE: The aim of the current study was to perform nucleotide sequencing of 5' UTR region for genotyping of viral isolates circulating in Peshawar, Pakistan. METHODS: The total number of commercially untypable samples were 94 in which 18 samples were sequenced for the characterization of 5' UTR region. Post-sequencing analysis was performed for genotype identification (n = 18) and molecular phylogenetic analysis. RESULTS: The current study reveals different genotypes, that is, 10/18 viral isolates were found to be genotype 3a (55.55%), 3 isolates (genotype 3b, 16.66%), 2 isolates (genotype 6h/6g, 11.11%), 2 (6g/d, 11.11%), and 1 sample (genotype 1c, 5.55%). In addition, genotype 3a is the dominant representative of HCV circulating in Pakistan and has been increasing across the country. CONCLUSION: The current study also reveals that genotype 6 (2 were genotype 6h/6g and 2 were 6g/d) is also circulating in Pakistan and not restricted to South China and Hong Kong.

Survey: smartphone-based assessment of cardiovascular diseases using ECG and PPG analysis.

A number of resources, every year, being spent to tackle early detection of cardiac abnormalities which is one of the leading causes of deaths all over the Globe. The challenges for healthcare systems includes early detection, portability and mobility of patients. This paper presents a categorical review of smartphone-based systems that can detect cardiac abnormalities by the analysis of Electrocardiogram (ECG) and Photoplethysmography (PPG) and the limitation and challenges of these system. The ECG based systems can monitor, record and forward signals for analysis and an alarm can be triggered in case of abnormality, however the limitation of smart phone's processing capabilities, lack of storage and speed of network are major challenges. The systems based on PPG signals are non-invasive and provides mobility and portability. This study aims to critically review the existing systems, their limitation, challenges and possible improvements to serve as a reference for researchers and developers.

Correction to: Survey: smartphone-based assessment of cardiovascular diseases using ECG and PPG analysis.

An amendment to this paper has been published and can be accessed via the original article.

Severity and relation of primary dysmenorrhea and body mass index in undergraduate students of Karachi: A cross sectional survey.

OBJECTIVE: To determine the frequency of primary dysmenorrhea and its association with body mass index in female students. METHODS: The cross-sectional study was conducted from January to March, 2018, in two districts of Karachi, and comprised female undergraduate students aged 15-25 years who had reached menarche at an appropriate age. A semi-structured questionnaire was used to assess dysmenorrhea while Seca scale was used for nutritional status. The association between body mass index and dysmenorrhea was worked out statistically using SPSS 23. RESULTS: Of the 410 students approached, 384(93.6%) responded. They had a mean age of 21±5.2 years. Dysmenorrhea was mild in 150(39%) subjects, 145(37.8%) moderate and 89(23.2%) severe. Overall, 273(71.1%) subjects had reached menarche aged 8-13 years. Dysmenorrhea was associated with radiating pain in 265(69%) and vomiting in 111(28.9%) subjects. Nutritional status was normal in 235(61.2%) subjects, 88(22.9%) were underweight, and 61(15.9%) were overweight and obese. Significant difference was observed in dysmenorrhea among underweight students (p<0.05). Age ?21 years also had a significant association with dysmenorrhea (p<0.05). CONCLUSION: Dysmenorrhea was found to have a significant association with body mass index and age.

A comprehensive review on past, present and future aspects of canine theileriosis.

Canine theileriosis is a notorious tick borne piroplasmid infection of wild and domestic canines. The causative agent has not yet been accurately classified. PCR studies revealed that causative agent resembles to Theileria genus and thus provisionally named as Theileria annae. The other Theileria species reported in canines is Theileria annulata, Theileria equi and unnamed Theileria specie. This emergent canine infection is considered to be endemic in most of the European countries. However in Asia this disease has not been reported till date. The vectors responsible for transmission of this disease have not been determined. It has been suggested that DNA of Theileria annae has been detected in hard tick Ixodes hexagonus in Northwestern Spain and several other tick species. Clinically canine theileriosis is characterized by severe weakness, fever, hemoglobinuria and anemia. Recently atovaquone or buparvaquone plus azithromycin therapy showed better clinical efficacy. This comprehensive review is intended to summarize the current knowledge on prevalence and epidemiology of canine theileriosis in different countries of the world and associated tick vectors.

New flavonoids from the Saudi Arabian plant Retama raetam which stimulates secretion of insulin and inhibits α-glucosidase.

Retama raetam is a bush which is a member of the family Fabaceae. It is used traditionally in North Africa and Saudi Arabia for the treatment of diabetes. Several flavonoids and alkaloids are already known from this plant. Chromatographic fractionation and purification led to the isolation of three new derivatives of prenylated flavones, retamasin C-E, and four new derivatives of prenylated isoflavones, retamasin F-I, in addition to two isoflavones which have not been previously reported in this plant. Particularly interesting structures included isoflavones containing 3,5-dihydro-2H-2,5-methanobenzo[e][1,4]dioxepine and 3a,8b-dihydro-7-hydroxyfuro[3,2-b]benzo[2,1-d]furan units, both of which are new amongst natural product flavonoids. Five new examples (two flavones and three isoflavones) strongly enhanced the glucose-triggered release of insulin by murine pancreatic islets and one isoflavone was a potent inhibitor of α-glucosidase. This study may rationalise the traditional medicinal use of R. raetam and provide new leads for drug design in the treatment of diabetes.

Carbazole and hydrazone derivatives as new competitive inhibitors of tyrosinase: Experimental clues to binuclear copper active site binding.

In this work a total of 12 carbazoles and hydrazone-bridged thiazole-pyrrole derivatives have been identified as new competitive inhibitors of tyrosinase. Carbazole derivative with 2-benzoimidazole substitution showed most potent inhibition in the series. Other carbazole derivatives containing benzothiazole and benzoxazole substitutions showed comparable levels of tyrosinase inhibition. The hydrazone derivatives also showed potent tyrosinase inhibitory activity with comparable Ki values except one with fluoride at its terminal position. Kinetic studies showed competitive inhibition of tyrosinase by all compounds that increased the substrate Km without changing the Vmax value. Moreover, experimental evidence suggests that the target compounds specifically bind to the binuclear copper center of the tyrosinase active site in an apparent mono-dentate fashion. Carbazoles and hydrazones are new and emerging classes of compounds as tyrosinase inhibitors that may provide new structural avenues to discovery of drugs targeting the treatment of hyperpigmentation and related dermatological disorders.

Natural flavonoid α-glucosidase inhibitors from Retama raetam: Enzyme inhibition and molecular docking reveal important interactions with the enzyme active site.

Retama raetam (Forsk.) Webb & Berthel plant has been traditionally used for the treatment of diabetes mellitus and hypertension. Interest in the medicinal chemistry of the plant in the past resulted in the isolation of a number of compounds with anti-hyperglycemic activity. The current work is a further extension of our recent work in which we isolated and characterized seven new flavonoids from Retama raetam with preliminary biological activity screening. It addresses the α-glucosidase inhibitory activity and molecular docking studies of the flavonoids. Retamasin D, G, H, and erysubin A and B noncompetitively inhibited the enzyme whereas retamasin C and F exhibited competitive inhibition. Moreover, retamasin C, F, G, and erysubin A and B carry dual activity in addition to α-glucosidase inhibition. Our previous studies have shown that they also caused significant stimulation of insulin from the blood-perfused pancreatic islets of Langerhans of mice. The C6 and C8 substituent groups greatly influenced the inhibition potency of the compounds. The most potent inhibitor was retamasin H with the γ-lactone ring substituent at C6 position of the main flavonoid moiety. Notable active chemical groups in the target compounds include γ-lactone, dihydropyran and dihydrofuran rings with hydroxyl and geminal methyl groups. Molecular modeling studies revealed that the compounds fit well in the α-glucosidase active site by interacting with important active site residues. These findings will incorporate new chemical, structural and functional diversity to the search and drug development of α-glucosidase inhibitors as anti-diabetic drugs.

Enzyme-Based Antiviral Potential of Cinnamomum verum J. Presl. Essential Oil and Its Major Component (E)-Cinnamaldehyde.

In the present study, Cinnamomum verum J. Presl. bark essential oil and its main component cinnamaldehyde was evaluated in vitro for neuraminidase (NA), transmembrane serine protease (TMPRSS2), and angiotensin converting enzyme 2 (ACE2) inhibitory activities. The chemical composition of C. verum essential oil was confirmed by both gas chromatography-mass spectrometry (GC/MS), and gas chromatography-flame ionization detection (GC-FID), where 75.9% (E)-cinnamaldehyde was the major component. The ACE2, NA, and TMPRSS2 enzyme inhibitions of C. verum bark essential oil at 20 µg/mL concentration, and (E)-cinnamaldehyde (5 µg/mL) were calculated and compared in the range of 54.2-89.9%. Molecular docking results supported that (E)-cinnam-aldehyde was specific to ACE2 with 89.9% inhibition. Our findings suggest further in vivo studies to confirm the effective and safe use of the essential oil as well as the (E)-cinnamaldehyde.